Myofibroblasts are a unique class of cells critical in normal human organogenesis and wound repair. Dysregulation of the normal mechanisms of myofibroblast apoptosis are proposed to play a role in the development of fibroproliferative diseases such as idiopathic pulmonary fibrosis. The goal of this proposal is to elucidate the mechanisms that allow myofibroblasts to be eliminated at the completion of normal wound repair when growth factor levels decline. We hypothesize that (i) death receptor activation with its resultant caspase-8 and effector caspase activation is necessary for growth factor withdrawal-induced apoptosis and that (ii) the p53 tumor suppressor gene modulates the apoptotic signal through its effects on death receptor and death ligand expression, and the Bcl-2 family of proteins. These hypotheses will be tested in a transformed lung myofibroblast cell line and in primary cultured murine myofibroblasts. Ultimately, the techniques, strategies, and results of these studies can be applied to a range of fibroproliferative diseases and serve as a basis for developing novel pharmacological targets for new therapies for fibrotic lung diseases.